It is well known that the availability of fatty acids for oxidation at the cellular level might be responsible for alterations in carbohydrate metabolism. While some in vivo studies have demonstrated that changes in plasma free fatty acids are accompanied by reciprocal changes in whole body glucose oxidation it has not been fully established how insulin mediated glucose disposal may be related to changes in endogenous lipid metabolism in man. This study combines the techniques of the euglycemic clamp, indirect calorimetry, and labelled free fatty acid infusion in order to examine the relationship between insulin mediated glucose disposal, carbohydrate oxidation and storage and measures of lipid metabolism including free fatty acid turnover and lipid oxidation. In vitro adipocyte lipolysis was also assessed from adipocytes isolated from an open fat biopsy from the same subjects. Subjects were studied over a wide range of obesity in order to provide a range of lipid metabolic profiles and insulin resistance. The data suggested direct interaction between lipid oxidation and glucose oxidation in vivo. However this interrelationship can only partially explain impaired in vivo insulin mediated glucose disposal, since the disposal of glucose involves a storage component which is of at least equal importance to oxidation and is not directly related to fatty acid metabolism.